In vivo alteration of the pathways of dopamine metabolism

Abstract

The 24-hour urine of normal fasting rats injected intraperitoneally with 300 µg of C¹⁴-labeled dopamine was found to contain an average of 39% of the administered radioactivity as unconjugated homovanillic acid (HVA), 3.4% as homoprotocatechuic acid (HPA), 6.5% as 3-methoxytyramine, and 6.1% as dopamine; 80% of the 3-methoxytyramine was conjugated as the glucuronide. Pretreatment with a monamine oxidase inhibitor resulted in a 10-fold reduction of HVA and HPA excretion and a 3-fold increase in 3-methoxytyramine excretion without affecting the excretion of dopamine. Pretreatment with a catechol-O-methyl transferase inhibitor reduced 3-methoxytyramine excretion to negligible amounts, increased HPA excretion fivefold without affecting HVA or dopamine excretion significantly. The ratio of labeled 3-methoxytyramine to labeled HVA after the injection of 200 µg of labeled 3-methoxytyramine was 0.81, from which it was calculated that 21% of the HVA excreted after an exogenous load of dopamine was derived from the 3-methoxytyramine pathway and 79% was derived from the HPA pathway. An unidentified metabolite was found in the catecholamine fraction of urine after monamine oxidase inhibition and after pretreatment with ethanol (1.9 and 1.1% of the administered dose, respectively).